Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.

The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34(+)) leukemic versus normal specimens.

BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells.

Most forms of chemotherapy employ mechanisms involving induction of oxidative stress, a strategy that can be effective due to the elevated oxidative state commonly observed in cancer cells. However, recent studies have shown that relative redox levels in primary tumors can be heterogeneous, suggesting that regimens dependent on differential oxidative state may not be uniformly effective. To investigate this issue in hematological malignancies, we evaluated mechanisms controlling oxidative state in primary specimens derived from acute myelogenous leukemia (AML) patients.

Disease-related anemia in chronic lymphocytic leukemia is not due to intrinsic defects of erythroid precursors: a possible pathogenetic role for tumor necrosis factor-alpha.

Background/aims: Disease-related anemia in chronic lymphocytic leukemia (CLL) occurs when the obvious causes are excluded while its pathogenesis is still obscure. We investigated its underlying mechanisms in 56 untreated patients with CLL.

Methods: Bone marrow (BM) lymphocytic infiltration was estimated in trephine biopsies.

Horizontal DNA and mRNA transfer between donor and recipient cells after allogeneic hematopoietic cell transplantation?

Allogeneic hematopoietic cell transplantation in humans results in true biological chimeras. There is now accumulating evidence that besides Graft versus Host Disease (GvHD), there are also other consequences in the co-existence of two genetically distinct populations in the transplant recipient. First, epithelial cells with donor-derived genotype emerge.